Actin-bundling protein TRIOBP forms resilient rootlets of hair cell stereocilia essential for hearing

Shin Ichiro Kitajiri, Takeshi Sakamoto, Inna A. Belyantseva, Richard J. Goodyear, Ruben Stepanyan, Ikuko Fujiwara, Jonathan E. Bird, Saima Riazuddin, Sheikh Riazuddin, Zubair M. Ahmed, Jenny E. Hinshaw, James Sellers, James R. Bartles, John A. Hammer, Guy P. Richardson, Andrew J. Griffith, Gregory I. Frolenkov, Thomas B. Friedman

Research output: Contribution to journalArticlepeer-review

153 Scopus citations

Abstract

Inner ear hair cells detect sound through deflection of mechanosensory stereocilia. Each stereocilium is supported by a paracrystalline array of parallel actin filaments that are packed more densely at the base, forming a rootlet extending into the cell body. The function of rootlets and the molecules responsible for their formation are unknown. We found that TRIOBP, a cytoskeleton-associated protein mutated in human hereditary deafness DFNB28, is localized to rootlets. In vitro, purified TRIOBP isoform 4 protein organizes actin filaments into uniquely dense bundles reminiscent of rootlets but distinct from bundles formed by espin, an actin crosslinker in stereocilia. We generated mutant Triobp mice (TriobpΔex8/Δex8) that are profoundly deaf. Stereocilia of TriobpΔex8/Δex8 mice develop normally but fail to form rootlets and are easier to deflect and damage. Thus, F-actin bundling by TRIOBP provides durability and rigidity for normal mechanosensitivity of stereocilia and may contribute to resilient cytoskeletal structures elsewhere.

Original languageEnglish
Pages (from-to)786-798
Number of pages13
JournalCell
Volume141
Issue number5
DOIs
StatePublished - May 2010

Bibliographical note

Funding Information:
The authors thank M. Ikeya for advice and vectors, M. Streuli for mononclonal antiserum to TRIOBP-1/5, P. Belyantsev for drawings, and N. Gavara, M. Barzik, R. Chadwick, J. Schultz, and D. Drayna for discussions. This work was supported by NIDCD/NIH R01DC008861 and R01DC009434 to G.I.F., R01 DC004314 to J.R.B., the Wellcome Trust grant 071394/Z/03/Z to G.P.R., the HEC and MoST, Islamabad to S.R., intramural programs of NIDDK, NHLBI, and NIDCD Z01 DK060100 to J.E.H., Z01 DK060100 to J.A.H., Z01 HL004232-08 to J.S., Z01 DC 000064 to A.J.G., and Z01 DC000048 to T.B.F.

Keywords

  • Cellbio
  • Humdisease
  • Molneuro

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

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